The enzyme indoleamine 2,3-dioxygenase (also known as INDO or IDO) degrades the indole moiety of tryptophan, serotonin, and melatonin, and initiates the production of neuroactive and immunoregulatory metabolites, collectively known as kynurenines. By locally depleting tryptophan and increasing proapoptotic kynurenines, IDO can greatly affect T-cell proliferation and survival. IDO induction could be a common mechanism of deletional tolerance driven by regulatory T cells. These responses are expected to operate in a variety of physiopathological conditions.
IDO has been shown to play a role in immunosuppression, tumor resistance and/or rejection, chronic infections, HIV-infection, AIDS (including its manifestations such as cachexia, dementia and diarrhea), autoimmune diseases or disorders (such as rheumatoid arthritis), and immunologic tolerance and prevention of fetal rejection in utero. Inhibitors of IDO can be used to activate T cells and therefore enhance T cell activation when the T cells are suppressed by pregnancy, malignancy, or a virus such as HIV. Inhibition of IDO may also be an important treatment strategy for patients with neurological or neuropsychiatric diseases or disorders such as depression. Accordingly, therapeutic agents aimed at suppression of tryptophan degradation by inhibiting IDO activity are desirable. The compounds, compositions, and methods described in the present application address the current need for IDO inhibitors.